The Prevalence of Phenylketonuria (Pku) and Hyperphenylalaninemia (Hpa) in Iran: A Systematic Review and Meta-Analysis Publisher Pubmed



Faraji S ; Tabatabaee Jabali SM ; Abolhasani MH ; Amirkashani D ; Haghdoost A ; Shadnoush M ; Talebi S ; Ranjbar G ; Talebi S ; Mahmoudi M ; Eshraghi P ; Najafimoghadam T ; Lesani Gouya B ; Nematy M Show All Authors
Source: Orphanet Journal of Rare Diseases Published:2026

Abstract

Background: Phenylketonuria (PKU) is one of the common Inborn Errors of Metabolism diseases, that is caused by a phenylalanine hydroxylase (PAH) deficiency or cofactor tetrahydrobiopterin. This systematic review and meta-analysis aimed to investigate the prevalence of PKU in Iran. Methods: The protocol was registered in PROSPERO (CRD42024540811). The MOOSE protocol and the PRISMA guidelines were used. The Web of Sciences, PubMed/ Medline, Sciences Direct, Google Scholar, Scopus, Civilica, IranDoc, and SID databases were searched on 31/03/2024. The I2 index and Q test were used to check heterogeneity. Comprehensive meta-analysis software (CMA ver. 2) was used (P < 0.05 is considered significant). The prevalences were reported in 100,000 neonates at national and provincial levels. Results: Finally, 20 studies with 1,992,090 Iranian neonates were included. The prevalence of screen-positive cases was 75.6 (95% CI: 48.1–118.72). The prevalence of confirmed PKU was 16.7 (95% CI: 13.6– 20.5); this prevalence in girls and boys was 15.2 (95% CI: 5.2–44.2) and 9.8 (95% CI: 3.2– 29.8), respectively. 53% of the cases had Hyperphenylalaninemia (HPA). The prevalence of HPA and classical PKU was estimated at 8.9 (95% CI: 5.9–13.41) and 8.0 (95% CI: 5.1–12.59), respectively. Subgroup analysis was performed based on region, province, and study quality to discover the source of heterogeneity. In addition, mixed effects meta-regression was used to find the relationship between continuous variables. Sensitivity analysis showed that the pooled estimate was robust. Conclusions: It seems that the screening program in Iran was effective and detected almost all PKU cases in the first few days of their lives. This information showed that the PKU prevalence is relatively higher than in most parts of the world, thus their prevalence should be controlled. © The Author(s) 2026.